Background: Type 2 myocardial infarction is caused by myocardial oxygen supply-demand imbalance, and its diagnosis is increasingly common with the advent of high-sensitivity cardiac troponin assays. Although this diagnosis is associated with poor outcomes, widespread uncertainty and confusion remain among clinicians as to how to investigate and manage this heterogeneous group of patients with type 2 myocardial infarction. Methods: In a prospective cohort study, 8064 consecutive patients with increased cardiac troponin concentrations were screened to identify patients with type 2 myocardial infarction. We excluded patients with frailty or renal or hepatic failure. All study participants underwent coronary (invasive or computed tomography angiography) and cardiac (magnetic resonance or echocardiography) imaging, and the underlying causes of infarction were independently adjudicated. The primary outcome was the prevalence of coronary artery disease. Results: In 100 patients with a provisional diagnosis of type 2 myocardial infarction (median age, 65 years [interquartile range, 55–74 years]; 43% women), coronary and cardiac imaging reclassified the diagnosis in 7 patients: type 1 or 4b myocardial infarction in 5 and acute myocardial injury in 2 patients. In those with type 2 myocardial infarction, median cardiac troponin I concentrations were 195 ng/L (interquartile range, 62–760 ng/L) at presentation and 1165 ng/L (interquartile range, 277–3782 ng/L) on repeat testing. The prevalence of coronary artery disease was 68% (63 of 93), which was obstructive in 30% (28 of 93). Infarct-pattern late gadolinium enhancement or regional wall motion abnormalities were observed in 42% (39 of 93), and left ventricular systolic dysfunction was seen in 34% (32 of 93). Only 10 patients had both normal coronary and normal cardiac imaging. Coronary artery disease and left ventricular systolic dysfunction were previously unrecognized in 60% (38 of 63) and 84% (27 of 32), respectively, with only 33% (21 of 63) and 19% (6 of 32) on evidence-based treatments. Conclusions: Systematic coronary and cardiac imaging of patients with type 2 myocardial infarction identified coronary artery disease in two-thirds and left ventricular systolic dysfunction in one-third of patients. Unrecognized and untreated coronary or cardiac disease is seen in most patients with type 2 myocardial infarction, presenting opportunities for initiation of evidence-based treatments with major potential to improve clinical outcomes. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03338504.

Background: Whilst the 99th percentile is the recommended diagnostic threshold for myocardial infarction, some guidelines also advocate the use of higher troponin thresholds to rule-in myocardial infarction at presentation. It is unclear whether the magnitude or change in troponin concentration can differentiate causes of myocardial injury and infarction in practice. Methods: In a secondary analysis of a multi-centre randomized controlled trial, we identified 46,092 consecutive patients presenting with suspected acute coronary syndrome without ST-segment elevation myocardial infarction. High-sensitivity cardiac troponin I concentrations at presentation and on serial testing were compared between patients with myocardial injury and infarction. The positive predictive value (PPV) and specificity were determined at the sex-specific 99th percentile upper reference limit (URL), and rule-in thresholds of 64 ng/L and 5-fold of the URL for a diagnosis of type 1 myocardial infarction. Results: Troponin was above the 99th percentile in 8,188 (18%) patients. The diagnosis was type 1 or type 2 myocardial infarction in 50% and 14%, and acute or chronic myocardial injury in 20% and 16%, respectively. Troponin concentrations were similar at presentation in type 1 (median [25th percentile - 75th percentile] 91 [30-493] ng/L) and type 2 (50 [22-147] ng/L) myocardial infarction, and in acute (50 [26-134] ng/L) and chronic (51 [31-130] ng/L) myocardial injury. The 99th percentile and rule-in thresholds of 64 ng/L and 5-fold URL gave a PPV of 57% (95% confidence interval [CI] 56-58%), 59% (58-61%) and 62% (60-64%), and a specificity of 96% (96-96%), 96% (96-96%) and 98% (97-98%), respectively. The absolute, relative and rate of change in troponin concentration was highest in patients with type 1 myocardial infarction (P<0.001 for all). Discrimination improved when troponin concentration and change in troponin were combined compared to troponin concentration at presentation alone (area under curve, 0.661 [0.642-0.680] versus 0.613 [0.594-0.633]). Conclusions: Although we observed important differences in the kinetics, cardiac troponin concentrations at presentation are insufficient to distinguish type 1 myocardial infarction from other causes of myocardial injury or infarction in practice and should not guide management decisions in isolation. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01852123

Aims Whilst the risk factors for type 1 myocardial infarction due to atherosclerotic plaque rupture and thrombosis are established, our understanding of the factors that predispose to type 2 myocardial infarction during acute illness is still emerging. Our aim was to evaluate and compare the risk factors for type 1 and type 2 myocardial infarction. Methods and results We conducted a secondary analysis of a multi-centre randomized trial population of 48 282 consecutive patients attending hospital with suspected acute coronary syndrome. The diagnosis of myocardial infarction during the index presentation and all subsequent reattendances was adjudicated according to the Universal Definition of Myocardial Infarction. Cox regression was used to identify predictors of future type 1 and type 2 myocardial infarction during a 1-year follow-up period. Within 1 year, 1331 patients had a subsequent myocardial infarction, with 924 and 407 adjudicated as type 1 and type 2 myocardial infarction, respectively. Risk factors for type 1 and type 2 myocardial infarction were similar, with age, hyperlipidaemia, diabetes, abnormal renal function, and known coronary disease predictors for both (P &lt; 0.05 for all). Whilst women accounted for a greater proportion of patients with type 2 as compared to type 1 myocardial infarction, after adjustment for other risk factors, sex was not a predictor of type 2 myocardial events [adjusted hazard ratio (aHR) 0.82, 95% confidence interval (CI) 0.66–1.01]. The strongest predictor of type 2 myocardial infarction was a prior history of type 2 events (aHR 6.18, 95% CI 4.70–8.12). Conclusions Risk factors for coronary disease that are associated with type 1 myocardial infarction are also important predictors of type 2 events during acute illness. Treatment of these risk factors may reduce future risk of both type 1 and type 2 myocardial infarction.

Background: The 99th centile of cardiac troponin, derived from a healthy reference population, is recommended as the diagnostic threshold for myocardial infarction, but troponin concentrations are strongly influenced by age. Our aim was to assess the diagnostic performance of cardiac troponin in older patients presenting with suspected myocardial infarction. Methods: In a secondary analysis of a multicenter trial of consecutive patients with suspected myocardial infarction, we assessed the diagnostic accuracy of high-sensitivity cardiac troponin I at presentation for the diagnosis of type 1, type 2, or type 4b myocardial infarction across 3 age groups (<50, 50–74, and ≥75 years) using guideline-recommended sex-specific and age-adjusted 99th centile thresholds. Results: In 46 435 consecutive patients aged 18 to 108 years (mean, 61±17 years), 5216 (11%) had a diagnosis of myocardial infarction. In patients <50 (n=12 379), 50 to 74 (n=22 380), and ≥75 (n=11 676) years, the sensitivity of the guideline-recommended threshold was similar at 79.2% (95% CI, 75.5–82.9), 80.6% (95% CI, 79.2–82.1), and 81.6% (95% CI, 79.8–83.2), respectively. The specificity decreased with advancing age from 98.3% (95% CI, 98.1–98.5) to 95.5% (95% CI, 95.2–95.8), and 82.6% (95% CI, 81.9–83.4). The use of age-adjusted 99th centile thresholds improved the specificity (91.3% [90.8%–91.9%] versus 82.6% [95% CI, 81.9%–83.4%]) and positive predictive value (59.3% [57.0%–61.5%] versus 51.5% [49.9%–53.3%]) for myocardial infarction in patients ≥75 years but failed to prevent the decrease in either parameter with increasing age and resulted in a marked reduction in sensitivity compared with the use of the guideline-recommended threshold (55.9% [53.6%–57.9%] versus 81.6% [79.8%–83.3%]. Conclusions: Age alters the diagnostic performance of cardiac troponin, with reduced specificity and positive predictive value in older patients when applying the guideline-recommended or age-adjusted 99th centiles. Individualized diagnostic approaches rather than the adjustment of binary thresholds are needed in an aging population.